Reshapable Device for Fixation at a Dental Site

ABSTRACT

A reshapable retention device for insertion at a dental site and contact with adjacent dental surfaces, for the controlled delivery to the dental site of at least one material having a predetermined intraoral activity. The retention device comprises at least one matrix containing the material. The retention device is adapted for physically affixing at the dental site for at least a predetermined time period correlated to the delivery of a predetermined portion of the at least one matrix to the dental site in a controlled single, bi or multiphase pattern. The retention device comprises a first configuration in which the overall dimensions of the retention device are larger than at least one dimension of the dental site. The first configuration is reshapable to a second configuration in which at least one dimension of the retention device is reduced to enable physically affixing the retention device at the dental site. In the second configuration the retention device comprises a predetermined shape having contours for affixing at the dental surfaces.

REFERENCE TO CO-PENDING APPLICATIONS

This application claims priority as a continuation of U.S. patentapplication Ser. No. 12/938,692, filed on Nov. 3, 2010 (now allowed),which in turn is a continuation of U.S. patent application Ser. No.11/890,986, filed on Aug. 8, 2007 (now U.S. Pat. No. 7,850,453), thecontents of which are each incorporated herein by reference in theirentireties.

FIELD OF THE INVENTION

The present invention relates generally to oral devices. In particular,the present invention relates to oral devices for retention at dentalsites within the intraoral cavity to enable, inter alia, any one of theprevention, treatment, diagnosis, elimination, and retardation of oraland other diseases or problems. More particularly, the present inventionrelates to the chemical treatment of dental surfaces, or for chemicaland/or physical restoration of teeth. Even more particularly the presentinvention is directed at the delivery of fluoridizing and other agentsto or from interproximal sites among others.

BACKGROUND OF THE INVENTION

A significant percentage of dental caries (demineralization, decay)occurs between teeth (interproximally, aproximally). This difficult,inaccessible region has been recognized as a problem for more than halfa century. Approaches have ranged from grinding of the interproximalsurfaces to make them self-cleansing and thus caries “immune” (Mjor, I.A. Quintessence Int. 29: 600-602, 1998) to flossing between the teethwhich requires fastidious patient compliance and smooth surfaces. Theinclusion of fluoride (U.S. Pat. No. 4,638,823) and other agents indental floss (U.S. Pat. No. 5,875,799) and other electric (U.S. Pat. No.5,579,786) or mechanical and chemical devices (U.S. Pat. Nos. 4,576,190,4,638,823 and 5,373,599) does not appear to have significantly reducedinterproximal caries. There is thus, a need to develop a technique ordevice which overcomes these limitations and the disadvantages offlossing between the teeth.

Various means of chemically preventing or treating such lesions, as wellas other problems such as discoloration and sensitivity are described bythe inventors of the present invention in U.S. Pat. No. 7,118,376 andits co-pending US Continuation In Part Application, Publication No.2005-0175959, the contents of which, including publications referencedtherein, is fully incorporated herein by reference.

In U.S. Pat. No. 7,118,376 the inventors of the present invention,describe a system for the controlled delivery of at least one materialhaving a predetermined intraoral activity to an interproximal site of atleast one dental surface in an oral cavity. The system comprises apolymeric matrix containing the said material. The system issufficiently flexible for insertion at the interproximal site to bephysically affixed thereat and sufficiently tough to maintain mechanicalintegrity at the interproximal site for the required amount of time andfor a predetermined amount of time. The interproximal site is defined inU.S. Pat. No. 7,118,376 as an area of contact and surrounding surfacesbetween the dental surface and an adjacent dental surface. Theco-pending US Continuation In Part Application, Publication No.2005-0175959, discloses the delivery of a predetermined portion of theat least one matrix to the interproximal site in a controlled single, bior multiphase pattern.

However, the system described in U.S. Pat. No. 7,118,376 and itsco-pending US Continuation In Part Application, Publication No.2005-0175959 is not directed to gingival and periodontal disease, or tothe general systemic treatment or prevention related to the oral cavityand digestive system. Moreover, they do not relate to subtle anatomicnuances of the dentition and gingival and periodontal tissue in healthyor pathologic states.

The restoration of interproximal cavities, for example dental fillingprocedures, requires packed filling material to be retained in positionin a tooth for a period of time. A thin flexible strip made of metal,plastic or other suitable material, known as a dental matrix band (orband, or matrix) is typically wrapped around the sides of the toothbeing restored to maintain the filling in place while and after thefiling has been placed to prevent the filling from distorting or flowingout of the desired tooth contour. Thus, a matrix band acts as a templateto facilitate reestablishment of lost tooth contour by the fillingmaterial. A small wedge is often used, lodged in the interproximal spacebetween the band and adjacent tooth to urge the band into close contactwith the tooth being restored, and thus ensure that the band is heldproperly in place. A retention device that is fine tuned to anatomicalnuances of the interproximal site and that limits and avoids the needfor a wedge will facilitate proper placement of the matrix band at theinterproximal site without encroaching on and/or causing damage to thegingiva or at least limiting such damage. Moreover, a retention devicethat itself acts as a template to facilitate reestablishment of losttooth contour by the filling material may minimize costs involved withsuch procedures by reducing the amount of time and maximizing efficiencyof the procedure.

It is therefore an object of the present invention to provide aretention device for physically affixing at a dental site.

An additional object of the present invention is to provide a reshapabledevice for physically affixing at a dental site to have a desired orpredetermined activity to at least one desired dental surface in theoral cavity, or into the oral cavity, which overcomes the disadvantagesof the prior art.

It is another object of the present invention to provide such a devicethat is particularly directed to the anatomical areas of interproximalsites and furcations.

It is yet another object of the present invention to provide a systemfor fixing a plurality of devices intraorally.

It is a further object of the present invention to provide such a devicethat is configured according to the contours of dental and soft tissuesurfaces.

It is still another object of the present invention to provide such adevice that employs at least one matrix as a carrier for activematerial.

It is an additional object of the present invention to provide such adevice in which the matrix for the active material may be biodegradable,resorbable or non-resorbable.

It is another object of the present invention to provide such a devicewhich is particularly adapted for physical fixation at a dental site,for at least a predetermined time period, typically sufficient to enablethe controlled or sustained delivery of a required quantity of theactive material from the matrix or matrices to the surfaces and/or oralcavity.

It is another object of the present invention to provide such a devicein which the physical affixing of the device is by way of a physicalproperty of the matrix, in particular wherein the matrix comprises ahydrophilic polymer which softens and swells in situ by the hydrationthereof in the oral cavity after accommodation at the dental site.

It is another object of the present invention to provide such a devicewhich is adapted on the one hand to accommodate the matrix and align thesame with the dental site, and on the other hand is also adapted foraffixing at the site by virtue of its shape, configuration andelasticity/resilience of the material from which it is made. Inparticular, such adaptation includes sufficient elasticity and toughnessof the matrix material, which are important criteria when positioningthe matrix between teeth.

It is another object to provide such a system wherein the device issufficiently flexible for insertion into an interproximal site, and atthe same time of sufficient toughness to maintain mechanical integritythereat, while being soft enough not to be a source of discomfort withinthe oral cavity prior to its removal or biodegration.

It is another object of the present invention to provide any one orcombination of a plurality of chemical and other agents that have adesired activity at the dental site, in particular such as to enableinter alia the cleaning, prevention, treatment, diagnosis, cosmetictreatment (whitening/bleaching and mouth/breath freshening), eliminationor retardation of dental caries at tooth surfaces or at tooth interfaceswith restorations or prostheses or to treat gingival or periodontaldisease.

It is another object of the present invention to provide a system thatis shaped to fit over a portion of, or an entire single dental arch.

It is another object of the present invention to provided such a devicethat is designed to release a chemical agent into the saliva for adesired or predetermined activity therewithin or in the digestive tractor absorption into the body.

It is another object of the present invention to provide such a devicewhich includes at least one adhering agent.

It is another object of the present invention to provide such a devicein a specific, controlled micro-environment which selectively excludesat least one element or molecule present in the mouth by way of aphysical or chemical property of the matrix or matrices.

It is another object of the present invention to provide such a devicein a specific, controlled micro-environment which optimizes the deliveryof a least one element, molecule or agent to the said dental site. Thesaid element, molecule or agent can be exogenous, from the device, orendogenous, e.g. directly or indirectly from the saliva.

It is another object of the present invention to provide such a systemthat employs at least one matrix to deliver a single phase controlledrelease pattern or a bi- or multiphase controlled release pattern todeliver at least one agent at an appropriate or optimal time, stage,manner or form.

It is another object of the present invention to provide such a systemthat employs at least one bi- or multi-layer or bi- or multi-locatedmatrix to provide a single phase, biphase or multiphase controlledrelease system.

It is another object of the present invention to provide such a systemthat employs at least one matrix which keeps the active material ormaterials inactive by chemical means such as inhibition or physicalseparation in order to allow at least one agent to be delivered at anappropriate or optimal time, stage, manner or form.

It is another object of the present invention that the device is adaptedto facilitate affixing at least one matrix band at the interproximalsite to restore at least one cavity.

It is another object of the present invention that the device itself isadapted physically or chemically to allow the restoration of at leastone interproximal cavity.

Additional objects and advantages of the present invention will becomeapparent as the description proceeds.

SUMMARY OF THE INVENTION

Thus, the present invention provides a method for the prevention and/ortreatment of dental caries in a patient in need thereof, comprisingapplying at a dental site of said patient the matrix or matricesaccording to the invention, wherein the material is a fluoridationagent. Said material is selected from the group consisting of sodiumfluoride, stannous fluoride, acidulated phosphate fluoride, calciumfluoride, an amine fluoride, fluoroaluminosilicate glass and any mixturethereof.

Alternatively, the material of the present invention is an amorphousmineral. Said material is selected from the group consisting ofamorphous calcium phosphate, amorphous calcium phosphate fluoride,amorphous calcium carbonate phosphate, amorphous calcium carbonatephosphate fluoride, amorphous calcium fluoride and dicalcium phosphatedehydrate.

Alternatively, the material of the present invention is a crystallinemineral. Said material is selected from the group consisting ofaragonite, brushite, calcite, dahltite, ferrhydrite, fluoro apatite,hydroxyapatite, lepidocrocite, magnetite, octocalsium phosphate,vaterite and whitlockite.

Alternatively, the material of the present invention is made of anorganic material. Said material is selected from the group consisting ofmacromolecules such as acidic proteins, glycoproteins or sulfatedpolysaccharides, or smaller molecules such as polyaspartic orpolyglutamic acid.

Alternatively, the material of the present invention is an enhancingagent or further active agent. Said material is selected from the groupconsisting of calcium chloride, calcium bromide, calcium nitrate,calcium acetate, calcium gluconate, calcium benzoate, calciumglycerophosphate, calcium formate, calcium fumarate, calcium lactate,calcium butyrate, calcium isobutyrate, calcium malate, calcium maleate,calcium propionate, calcium vaerate, alkali salts, ammonium salts oforthophosphoric acid such as potassium sodium or ammoniumorthophosphate, monopotassium phosphate, dipotassium phosphatetripotassium phosphate, monosodium phosphate, disodium phosphate andtrisodium phosphate.

Alternatively, the material of the present invention is an acidifying,buffering or pH regulating agent. Said material is selected from thegroup consisting of acidulated phosphate fluoride, citric acid, sodiumcitrate, sodium bicarbonate, calcium carbonate, arginine and polyacrylicacid fully neutralized with alkalimetal ammonium or (alkylol) aminecompound sodium polyacrylate.

Alternatively, the material of the present invention is an antimicrobialagent. Said material is selected from the group consisting of stannousfluoride, alexidine, chlorhexidine digluconate, hexetidine, copper zinccitrate and stannous pyrophosphate, triclosan, cetylpyridinium chlorideand halogenated bisphenolic compounds.

Alternatively, the material of the present invention serves as acleaning agent. Said material is selected from the group consisting ofsodium alkyl sulfate, sodium lauryl sulfate, sodium coconutmonoglyceride sulfonates, sodium lauryl sarcosinate, taurates, sodiumlauryl sulfoacetate, sodium lauroyl isothionate, sodium laurethcarboxylate, sodium dodecyl benzenesulfonate, poloxamers,polyoxyethylene sorbitan esters, fatty alcohol ethoxylates, polyethyleneoxide, cocamidoppropyl betaine, sodium bicarbonate, monosodiumphosphate,sodium hydroxide, potassium hydroxide, sodium carbonate and imidazole.

Alternatively, the material of the present invention serves as aneffervescing agent. Said material uses a sodium bicarbonate/citric acidsystem.

Alternatively, the material of the present invention serves as a toothdesensitizing agent. Said material is selected from the group consistingof fluorides, potassium citrate, potassium chloride, potassium tartrate,potassium bicarbonate, potassium oxalate and potassium nitrate.

Alternatively, the material of the present invention serves as a toothwhitening or bleaching agent. Said material is selected from the groupconsisting of hydrogen peroxide, carbamide peroxide metal chlorites,perborates, percarbonates, peroxyacids, persulfates, urea peroxide,calcium peroxide, calcium chlorite, barium chlorite, magnesium chlorite,lithium chlorite, sodium chlorite, potassium chlorite, hypochlorite,chlorine dioxide, sodium percarbonate, oxones, and protease.

BRIEF DESCRIPTION OF THE FIGURES

In the drawings:

FIG. 1( a) illustrates a side, elevation view of a lingual portion oftwo lower posterior teeth (a molar and bicuspid (premolar)), showing thespace between these two teeth (the interproximal or aproximal space),the gingival papilla and the contact area.

FIG. 1( b) illustrates a cross-sectional view taken along X-X of theembodiment of FIG. 1( a), showing the bicuspid (premolar) with thelingual interdental gingival papillae, the buccal (facial) interdentalgingival papillae, the contact area and the gingival col.

FIG. 2( a) illustrates a first embodiment of the retention device of thepresent invention in an H-shape.

FIG. 2( b) illustrates the retention device of FIG. 2( a) gripped alongthe centerline of the device by the tip of tweezers.

FIG. 2( c) illustrates the direction in which the retention device ofFIG. 2( a) is folded while being gripped along the centerline bytweezers.

FIG. 2( d) illustrates the retention device in a folded configuration.

FIG. 2( e) illustrates a side elevation view of a bucal portion of twolower posterior teeth similar to that shown in FIG. 1( a), showing thefolded retention device being inserted interproximally while beinggripped by tweezers.

FIG. 2( f) illustrates the folded retention device positionedinterproximally.

FIG. 3( a) illustrates a side elevation view of a bucal portion of twolower posterior teeth similar to that shown in FIG. 1( a) and FIG. 2(e), showing periodontal disease resulting in gingival and bonerecession, and showing a rolled retention device being inserted withtweezers into a furcation of a molar tooth.

FIG. 3( b) illustrates the rolled retention device in situ, positionedin the furcation.

FIG. 4( a) illustrates the retention device a configuration comprisingnotches (or, recesses) to facilitate interproximal placement around theinterdental gingival papilla, and extensions (or, protrusions) in orderto fill the col area and to overlap the gingival papilla on the exteriorportions.

FIG. 4( b) illustrates the retention device similar to that shown inFIG. 4( a), in an elongated form to fill an asymmetrical col area.

FIG. 4( c) illustrates the retention device shown in FIG. 4( a) withside flaps (or, wing members) which also facilitate retention at aninterproximal site and increases the area of contact of the device to alarger area around the contact area.

FIG. 4( d) illustrates the retention device in a star shapedconfiguration, similar in essence to that of FIGS. 4( c) and 4(d).

FIG. 4( e) illustrates the retention device in a C-shaped configuration,showing the axes about which the device may be folded to form asymmetrical (Y-Y) shaped device or asymmetrical (Z-Z) shaped device.

FIG. 5( a) illustrates a front view of the retention device in a Y-shapein an upside down orientation, which is anatomically contoured at thetwo apical portions, and slightly concaved at the portion forpositioning at the contact area.

FIG. 5( b) illustrates a cross-sectional view of the embodiment of FIG.5( a) taken along line XX-XX.

FIG. 5( c) is a side elevation view similar to FIG. 1( a) showing thedevice of FIG. 5( a) in situ—between the molar and bicuspid (premolar),which has a distal cavity in the bicuspid that requires a restoration.

FIG. 5( d) is a side elevation view similar to FIG. 1( a) showing amatrix band being held in situ by a Y-shaped retention device betweenthe molar and bicuspid (premolar) in order to facilitate restoration ofthe cavity.

FIG. 6( a) illustrates a frontal (facial) device view of a strip withtwo distal retention devices as shown in FIG. 4( c) in order to retainthe said strip between the first bicuspids (premolars) and canines bymeans of the retention devices which are attached to the strip by meansof an extension arm.

FIG. 6( b) illustrates a top view of the embodiment of FIG. 6( a) takenalong line YY-YY thereof.

FIG. 6( c) illustrates a top view of a longer strip that covers thefacial side of an entire dental arch with four retention systems.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is defined by the claims, the contents of whichare to be read as included within the disclosure of the specification,and will now be described by way of example with reference to theaccompanying Figures.

Throughout this specification and the claims which follow, unless thecontext requires otherwise, the word “comprise”, and variations such as“comprises” and “comprising”, will be understood to imply the inclusionof a stated integer or step or group of integers or steps but not theexclusion of any other integer or step or group of integers or steps.

The present invention relates to a device for the controlled orsustained delivery of a material or materials having a predeterminedintra-oral activity to dental surfaces of the oral cavity, typicallytooth surfaces or carious lesions, and in particular to interproximalsites or furcations, the device comprising a matrix or matricescontaining said material or materials. The matrix or matrices is adaptedfor the controlled or sustained release of the active material ormaterials, and is further adapted for physically affixing at the dentalsite, for at least a predetermined time period that is correlated to thedelivery of a predetermined portion of said material or materials tosaid site. This time period typically depends on the nature of theactive material or materials and on the subject being treated, and maycomprise a few seconds while a chemical activator, an electricalcurrent, or a heat or light source such as a laser is administered toabout four to eight hours during interproximal caries prevention ortreatment. It is to be appreciated that a major factor in establishingthe rate of release of the active material or materials is the structureof the polymeric matrix or matrices as a single uniform unit,multi-layer or a multi-location form. Thus, desired rates of release maybe achieved by employing specific polymers, which are preferablycross-linked to a degree affording the desired rate of release. Matricesthat are highly cross-linked would release the active material ormaterials more slowly, and vice versa. The man of skill in the art ofpharmacy and delivery system is familiar with such considerations, whichare described in many articles and textbooks, e.g., Remington'sPharmaceutical Sciences, Gennaro A. R. ed., Mack Publishing Company,Easton, Pa., 1990, which is fully incorporated herein by reference.

The release of an active agent or agents can be varied within a singlematrix or by utilizing a combination of more than one matrix. There aremany examples of means for varying release patterns from a singlematrix. Examples include different types and degrees of cross-linkageand different additives (such as antimicrobial agents, preservatives,sterilizing agents and enzyme inhibitors) which influence thebiodegradation. Furthermore, the release of even a single agent can varyby the manner it is bound in a matrix. For example, sodium fluoride canbe released from a single matrix in a biphasic manner where the initialrelease is of loosely bound sodium fluoride and the next release is ofmore firmly bound sodium fluoride. Different patterns can also beobtained by using different types of fluoride, for example sodiumfluoride, acidulated phosphate fluoride and an amino fluoride, whichdiffer chemically and in molecular size. Another facet is that thematrix can create a microenvironment which excludes some salivaryproducts such as proteins that inhibit mineralization, and others whichinclude mineralization such as calcium phosphate and arginine. Thebiphasic pattern of sodium fluoride release allows an initial burst offluoride ions to exchange with hydroxyapatite OH.sup.-groups andaccelerate remineralization, then the decrease of fluoride releaseallows the crystals to grow by providing some fluoride, calcium andphosphate from the matrix. The latter two elements can either be addedas agents to the matrix or absorbed by the matrix from the saliva. Thefinal release also favors the deposition of calcium fluoride globuleswhich are long term pH sensitive fluoride reservoirs.

Another approach of varying release patterns is the use of more than onematrix either as separate layers or multilocated systems. Besidescausing different release patterns, the use of more than one matrix cankeep different agents apart to in situ placement. Each matrix could beloaded with the same or different agent/s that could be released atdifferent rates and/or stages by utilizing intrinsically differentmatrices at the chemical level or/and physical parameters. For example,the outer layer of a bilayer sphere would first be exposed to the salivaand release, for example, an effervescent cleaning system which loosensand dislodges interproximal plaque and debris and then the inner layerreleases, for example, fluoride ions. Another example is the initialrelease of hypochlorite, which removes organic content of dentinaltubules and then a mineralizing agent or agents. (see Inaba D. et al.,Caries Res. 30:218-224 (1996).) Yet another example is that the devicecan comprise of a coronal and an apical region where the coronal regioncontains an agent or agents more effective on enamel and the apicalregion contains an agent or agents more effective on cementum, dentin,gingival and periodontal tissue. An example of a multilayeredmulti-phase release system is one designed to mimic chiton radulaformation which could be used to favorably alter tooth surfaces.

These matrices can comprise a single unit which was affixed one upon theother either by physical pressure or chemical bonding. They can also beformed by plating the first layer and then the same layer is plated overthe dried first layer.

The present invention more particularly relates to a retention devicefor affixing at a dental site within the intraoral cavity, and directedat the chemical treatment of dental surfaces at the site or for chemicaland/or physical restoration of the dental surfaces.

Referring to FIG. 1( a) showing a side, elevation view of a lingualportion of a molar (11) and a bicuspid (premolar) (12), and referring toFIG. 1( b) showing a cross-sectional view taken along X-X of FIG. 1( a),an interproximal site (13) is defined herein as comprising both the areaof contact (15) which is between two teeth on the medial and distaldental surfaces and the spaces surrounding area of contact (15) on thelingual (17) and buccal (facial) (18) sides of the area of contact (15),as well as at the coronal space (19) and the apical space (10). Theapical space (10) is bordered apically by interdental gingival papillae(141) and (142) on the lingual (141) and buccal (facial) (142) surfacesand by a valley known as the col (16), which is the central apical baseof the interproximal site (13), and which spans the interdental gingivalpapillae (14). The apical space (10) also includes the gingival sulcus(143) which surrounds the tooth (12) (see Glickman I ClinicalPeriodontology 4^(th) Ed. Saunders pg 18-19). The morphology and size ofthe above mentioned spaces are determined by the tooth size, positionand shape. For instance, the contact area in the posterior teeth islocated nearer the buccal surface (18) which causes a larger lingualgingival papilla (141). The contact area in anterior teeth is locatednearer the lingual surface, which causes a larger lingual papilla (seeGilmore H W et al, Operative Dentistry, 3^(rd) Ed., CV Mosby Company,pg. 25-26). Furthermore, the permanent anterior interdental papillarywidths are less than those of the permanent molars which range fromabout 14 mm to 5 mm. Obviously, primary (milk) teeth also have smallerinterdental papillary width dimensions. Additionally, diseases can alsocause variations in shape and size. For example, periodontal diseaseincreases the size of the spaces because of gingival and bone loss,however, on the other hand, spaces can be reduced due to gingivalswelling.

It should be noted that the contact area is erroneously referred to inconventional literature as a contact point, like two marbles makingcontact. This is often not the case, since attrition causes the contactto flatten, and the teeth to move, which results in a contact area ofabout 0.3-1.0 mm² in the posterior teeth, and smaller areas in anteriorand milk teeth. (see Gilmore H W, et al, op cit.)

The term, “dental surface” is defined herein as referring to any portionof a tooth or portion of the gingiva, particularly at interproximalsites and furcations.

The term, “reshape” as used herein refers to the act of reducing theoverall dimensions of an object, for instance by bending, folding,rolling or otherwise collapsing the object to a desired configuration(shape), physically or chemically. To that end, the terms, “collapsing”,“bending”, “folding”, “rolling”, etc. particularly refer to thereshaping of the device of the present invention to allow the device tofit in an area of a dental site that is smaller in at least onedimension than that of the device in its original shape (e.g. prior toreshaping).

The term, “dental site” as used herein refers in general tointerproximal sites and furcations. More specifically, the dental sitesreferred to herein comprise at least a space between adjacent dentalsurfaces, such that with reference to the interproximal site, the dentalsite includes at least a portion of the spaces (e.g. the apical space)surrounding the area of contact, and in some cases, includes the area ofcontact as well.

According to the present invention, in at least the reshapedconfiguration, the retention device is preferably shaped in ananatomical configuration according to the contours of the dentalsurfaces at the sites at which the device is affixed.

Thus, in a first aspect of the first embodiment of the presentinvention, and referring to FIGS. 2( a) to 2(f), the retention device(20) comprises a polymeric matrix containing an active material, and, inthe first aspect, has an H-shape. Retention device (20) is folded asdescribed herein below, for affixing at a dental site, typically belowarea of contact (15), and in some cases also at area of contact (15),depending on the morphology of the interproximal area, the rigidity ofthe device and operative procedures. Referring to FIG. 2( b), retentiondevice (20) may be gripped along its longitudinal centerline (or,bending line) (22) (see FIG. 2( a)) by the tip of thin tweezers (21).Since retention device (20) may be stiff (and cracked if bent when dry)tweezers (21) are preferably first dampened, for instance with a watersyringe from a dental unit or by dipping into a container of water priorto gripping, to allow retention device (20) to soften along the axisabout which the folding is performed. As seen in FIG. 2( c), whilegripping retention device (20) with tweezers, (21), the useradditionally holds the outer edges of retention device (20) with fingers(2), (4), and applies enough force to fold the outer edges toward eachother as indicated by arrows (220), thereby forming two flaps (23),(24), as shown in FIG. 2( d). Preferably, each outer edge is foldedinwards to form an angle of approximately 30.degree. between flaps (23),(24), however, retention device (20) may be folded more or less than30.degree., and may be rolled or folded over more than once, depending,among other things, on the size of the interproximal site. Referring toFIGS. 2( e) and 2(f), folded retention device (20′) is insertedinterproximally in an “A” (or, upside down “V”) orientation. Whenfixated interproximally, the apex of the “A” is situated below or atcontact area (15) of adjacent teeth (11), (12), and the outer surface offlaps (23), (24) rest along the mesial and distal tooth surfaces. Theinner surface of flaps (23), (24) arch over gingival (14). Whenabsorbing the moisture and fluids in the intraoral cavity, the devicesoftens and expands in situ, thereby causing device (20′) to essentiallyfill all or some of the space of the interproximal site (13).

FIGS. 3( a) and 3(b) show the first aspect of the first embodiment,wherein the retention device (20″) is in a rolled configuration forphysically affixing in a furcation (33) using a tweezer. FIG. 3 b showsrolled device HH physically fixed in the furcation (33) of the molar.When absorbing the moisture and fluids in the intraoral cavity, thedevice softens and expands in situ, thereby causing device (20″) toessentially fill all or some of the space of the furcation (33).

A second aspect of the first embodiment is shown in FIG. 4( a), in whichretention device (42) is shaped according to the contours of the apicalspace of the interproximal site. Retention device (42) comprisesslightly convex transverse edges (43) (although straight or concaveedges may be desirable in some cases), and longitudinal edges (44)comprising notches (or, recesses) (420) to accommodate the interdentalgingival papilla, and extensions (or, protrusions) (422) to enhanceretention at the dental surfaces, and a central extension (421) to fillthe col area and also enhance retention. Alternatively, extension (422)may be excluded, elongated or shortened, and the cross-sectional shapeneed not be straight but can be concave on one or both surfaces.Alternative shapes for conforming to the anatomy of different dentalsurfaces (e.g. interproximal sites) may be desired. For example,anterior and posterior spaces differ in size and in shape from eachother. Specifically, the posterior areas are wider, the position of thecol is not at the midpoint, and the buccal and lingual gingival papillaare not the same size. FIG. 4( b) illustrates an alternative aspect ofthe second aspect, wherein notch (424) is elongated to conform to theanatomy of posterior teeth interdental gingival papillae.

Furthermore, the second aspect can comprise the apical and coronalportion differing in shape. For example, the coronal portion can bestraight or dome shaped and the apical portion can be anatomicallyshaped, like that of FIGS. 4( a)-4(d).

FIG. 4( c) shows the second aspect of the first embodiment, wherein theretention device has wing members (430) for contacting the buccal andlingual tooth surfaces. Alternative structures may be used instead ofwing members to facilitate retention at the interproximal site, andincrease the contact of the retention device to a larger area around thecontact area.

FIG. 4( d) shows a third aspect, wherein retention device (40) is shapedin a star-shape, which is essentially similar to the embodiment shown inFIG. 4 a, but with concave edges, instead of convex edges, and which maybe reshaped for affixing at a dental site; FIG. 4( b) shows a fourthaspect, showing a C-shaped retention device (41) which can be folded,for example, along Y-Y to form a symmetrically folded device, or alongZ-Z to form an asymmetrically folded device. Other variations (notshown) include a star-shaped device that is elongated (i.e. stretched)in at least one plane.

Preferably according to all aspects of the first embodiment, retentiondevice is designed to facilitate bending or folding. For example, thebending line may be indented along the entire length, or indented orpunctured at intermittent points or lines (i.e. perforations) across atleast a portion of the length of the bending line. Alternatively, amarking such as a line may be situated along the surface of theretention device to indicate the preferred axis about which retentiondevice should be folded, for instance, in order to form the desiredflaps. This line can be a physical form of an area which has beenchemically treated to facilitate folded.

The present invention includes other aspects not shown in the figures ordescribed herein, such as a palette shape (see U.S. Design applicationsNo. 29/234,883 by the present inventors). Furthermore, the surfaces ofthe device may be flat, or one or more surfaces may be concave orconvex, or any combination thereof of shapes.

A second embodiment of the present invention, comprising all of theadvantages and features of the first embodiment, mutatis mutandis, isshown in FIGS. 5( a)-5(d), with the following differences. As seen inthe figures, particularly FIG. 5( b) showing a cross-sectional viewtaken along XX-XX of FIG. 5( a), retention device (50) is Y-shaped, forinserting and affixing in an upside down orientation at an interproximalsite (FIG. 5( c)) such that the elongated portion (51) is disposed atcontact area (513), and the “A” portion (515) is disposed beneathcontact area (513) of adjacent teeth (52), (53), wherein flaps (511),(512) contact adjacent dental surfaces. Flaps (511) and (512) aredesigned to be bent slightly towards one another in order to be placedinterproximally, whereafter flaps (511), (512) press slightly away fromone another towards adjacent dental surfaces, thereby enhancing fixationof retention device (50) at the interproximal site. Included in thisembodiment are modifications of the above description, for example, adevice that only incorporates the “A” portion (515), without elongatedportion (51).

According to one aspect of the second embodiment of the presentinvention and referring to FIGS. 5( c) and 5(d) retention device (50)can be made of a metal or plastic material for fixation at aninterproximal site, in order to facilitate the restoration of a cavity(54) with an appropriate restoration material such as a tooth coloredresin, glass ionomer or amalgam, independently, as shown in FIG. 5( c)or with a matrix band (55) as shown in FIG. 5( d). When flaps (511) and(512) push towards adjacent dental surfaces as described above,retention of matrix band (55) is facilitated.

A third embodiment of the present invention, comprising all of theadvantages and features of the first and second embodiments, mutatismutandis, is shown in FIGS. 6( a)-6(c), with the following differences.The third embodiment comprises a system of folded retention devices (62)attached directly or via at least one short or long extension arm (64)to an elongated strip (61) having the form of at least a portion of anentire dental arch, to allow a plurality of devices to be essentiallysimultaneously inserted to a dental site. FIG. 6( b) shows across-sectional view taken across line YY-YY of FIG. 6( a), showingstrip (61) covering the facial portion of anterior teeth (63). FIG. 6(c) shows a top view of a strip (65) corresponding to an entire dentalarch (65).

These applications are not limited to devices of a biodegradable,resorbable or non-resorbable nature nor any combination thereof whichare left in situ, but include devices that are activated or influencedby external means such as chemical or physical intervention. This formsa tough solid device at the site. An example of a physical applicationsuch as laser irradiation using CO₂ lasers, Nd:YAG lasers and Argonlasers.

The physical affixing of the device of the present invention is by wayof a physical property of the matrix, in particular wherein the matrixcomprises a hydrophilic polymer which softens and swells in situ by thehydration thereof in the oral cavity after accommodation at the dentalsite. The expansion can be designed to thicken (e.g. to 250%) in sizesubstantially more than it elongates (e.g. 20%), thereby not extrudingexcessively out of the interproximal and tooth domain. Optionally, theretention device comprises at least one adhesive surface or part thereofsuch as to enable the system to adhere or be fixed at a dental site.

Again, of course this invention is not limited to the above-describedembodiments, but encompasses all the variations thereof. It is alsoobvious to those schooled in the art that general toxicity, allergicresponses and pulp responses need to be investigated prior to applyingthe proposed techniques clinically.

In the system according to the present invention, the oral activityprovided by the active material or materials may be medical treatmentsuch as fluoridization, remineralization or mineralization anddesensitization and/or aesthetic treatment such as tooth whitening orproviding breath fresheners, and/or any other desired activity.

Thus, the different components of the matrix of the invention cancomprise a range of chemicals with the following functions:

The Primary Active Fluoridating Mineralization and/or RemineralizationAgents

The fluoride releasing agent/s and other mineralizing and remineralizingagent/s can be embedded within the polymeric matrix or matrices of theinvention, and released from there in a controlled or sustained mannerwith or without at least one auxiliary chemical or physical step forexample electrodes, sonification or laser application to the device insitu. The matrix or matrices described in this invention may comprise atleast one primary active fluoridizing mineralization and/orremineralization agent which provides fluoride and/or other ions, whichprimary agents can be divided into fluoridating agents and othermineralizing and/or remineralizing agents.

Fluoridation Agents

This agent may be any single or any combination of inorganic or organicfluoride-containing pharmaceutically acceptable chemicals known or to bedeveloped. These include, but are not limited to amine fluorides, e.g.olaflur [(N¹-octadecyl-trimethylendiamine-N,N,Ntris(2-ethanol)-2,2′-(3-n-(2-hydroxytheyl)octadecylamino]propyliminol)dihydrofloride]and dectaflur (9-octadecenylamine-hydrofluoride)), alexidinedihydrofluoride, hydrofluoride, ammonium fluoride, calcium fluoride,calcium carbonate monofluorophosphate, difluorosilane,fluoroaluminosilicate glass and any mixture thereof, hydrogen fluoride,fluoropolymer B (see U.S. Pat. No. 4,837,007), mixed salt neighborite(NaMgF3), magnesium fluoride, magnesium monofluorophosphate, potassiumfluoride, lithium fluoride, indium fluoride, zirconium fluoride, copperfluoride, nickel fluoride, palladium fluoride, potassiumfluorozirconate, tin fluorozirconate, sodium fluorozirconate, ammoniumfluorozirconate, fluorosilicate fluorozirconate, fluoroborates,fluorozirconate, fluorostannites, fluorozirconate, sodium fluoride,stannous fluoride, stannous hexafluorozirconate, sodiumhexafluorosilicate, sodium, lithium or potassium monofluorophosphatestrontium fluoride and ytterbium trifluoride. Preferably, the activemineralisation agent is sodium fluoride, and/or hydrogen fluoride. Thisinvention is not limited to the above but includes approaches such asthe corporation of fluoride in the form of Ca₅(PO₄)₃F (see U.S. Pat. No.4,556,561). Variations in pH and salt types of fluorides (e.g. stannous,ammonium, titanium and amino fluorides) result in different retention offluoride as calcium fluoride. For example, good results have beenobtained using fluoride at lower pH values such as ammonium fluoride(see Jenkins, G. N. The Physiology and Biochemistry of the Mouth p. 495,1978, Blackwell Scientific Publishing) and preferably thixotropicacidulated phosphate fluoride which can contain about 1-4% sodiumfluoride with or without 0.1-0.8% hydrogen fluoride and 0.5-1.5%orthophosphoric acid (see Craig, R. G. et al Dental Materials,Properties and Manipulation p2-28, 2^(nd) Ed. 1979 CV Mosby Co.)

The period of fluoride exposure which causes significant rehardening ofa demineralized enamel surface is about 4 hours (see Koulourides, T.,Art and Science of Dental Caries Research pp. 355-378, 1968; Poole, D.F. G. and Silverstone, L. M., Hard tissue Growth Repair andRemineralisation, pp. 35-52, Ciba Fondation Symposium No. 11, ElsevierScientific Publishing Company, 1973, Pearce E. I. F and Moore, A. J., J.Dent Res 64; 416-421, 1985). Obviously the period of fluoridationrequired is dependent on the type of material or device hereindescribed, its fluoride type and concentration, frequency and period ofdelivery, other chemical or physical interventions (such as current andlaser application) and the type of surface or lesion being treated.Furthermore, the effects can also be long term because of the depositionof pH controlled fluoride reservoirs of various CaF₂ forms.

The acute lethal dose of fluoride (F) is 33 mg F/Kg body weight and thechronic toxicity can be 0.1 mg F/Kg. Thus the determination of thefluoride concentration range is governed by the size and number ofdevices used or the volume of material used, the duration of applyingthe material or device, the rate of fluoride ion release and the weightof the patient. Thus the concentrations can range from about 7-0.2%.(See: A guide to the use of fluorides JADA 113:504-564, 1986, preparedby the National Fluoride Task force of the NFDH).

Mineralizing and/or Remineralizing Agents

Although fluoride is to date the most effective remineralization agent,this invention and practice thereof is not limited to fluoride alone butmay include or be limited to any other mineralizing or remineralizationagent known or to be developed or combination thereof. Examples areamorphous minerals, crystalline minerals and organic molecules.

An advantage of amorphous minerals is that they can be easy to mold intocomplex shapes (see Levi-Kalisman, Y. et al J. Chem. Soc. Dalton Trans2000: 3977-3982, 2000) such as pits and fissures, demineralized enamelor dentin. These amorphous minerals can be present in stable or unstablephases. Silica (opal) is a stable type which can be formed by thepolymineralization of silicic acid which can be mediated enzymatically.On the other hand amorphous calcium carbonate and amorphous calciumphosphate are unstable as they tend to transform into stable crystallinephases. Amorphous calcium phosphate, amorphous calcium phosphatefluoride, amorphous calcium carbonate phosphate, casein phosphopeptide,amorphous calcium phosphate nancomplexes, amorphous calcium carbonatephosphate fluoride, and amorphous calcium fluoride have highsolubilities, fast formation rates and fast conversion rates to apatite(see U.S. Pat. No. 5,460,803). This transformation can be controlled,for example by mimicking chiton teeth where amorphous calcium phosphateis converted into dahllite. Besides these agents there are other agentssuch as dicalcium phosphate dehydrate which complement fluoride inremineralizing carious lesions (Wefel, J. S, and Harless, J. D. J. DentRes 66: 1640-1643, 1987, Takagi, S. et al Caries Res 34: 281-288(2000)).

Examples of crystalline minerals are aragonite, brushite (see U.S. Pat.Nos. 3,679,360 and 5,605,677), calcite, dahltite, ferrihydrite,fluoroapatite, hydroxyapatite (which can also be used in dissolvedsynthetic forms) or in a stannous hydroxyapatite fluoride (see U.S. Pat.No. 4,923,683), lepidocrocite, magnetite, octocalcium phosphate,vaterite and whitlockite. This invention also includes a system designedto alter a tooth surface thereby enhancing its resistance to caries andother pathology. For example the process of chiton radula formation canbe fully or in part adapted to alter tooth surface clinically. Forexample iron atoms can be introduced which precipitate a hydratediron-oxide mineral, ferrihydrite which can then be converted tomagnetite or an iron oxide mineral, lepidocrocite. Another example isamorphous calcium phosphate which can be deposited and then induced tocrystallize to dahllite or hydroxyapatite (see Addadi, L. and Weiner, S.Angew, Chem. Int. Ed. Engl. 31:15, 3-169, (1992). Besideshydroxyapatite, an often found mineral at remineralized or mineralizedental sites is whitlockite (Kodaka, T. et al Caries Res 26: 69-76(1992). These amorphous or crystalline minerals can be used to restoredemineralized tissue such as interproximal caries or to seal regionssuch as pits and fissures by chemical or physical intervention (such aslaser application), to seal areas or alter the chemical surfacesthereof.

The organic material can be macromolecules such as acidic proteins,glycoproteins and sulfated polysaccharides (Addadi, L. and Weiner, S.Angew, Chem Int Ed Engl 31:153 169, (1992)) or smaller molecules such aspolyaspartic and polyglutamic acid with or without a rigid substrateadsorption (Addadi, L. et al ACS Sym. Series no. 444, 1991).

Enhancing or Other Active Agents

These agents can be the matrix or part thereof or added to the matrix(e.g. silated hydroxyethylcellulose as apatite is formed because silanolchelates calcium (see Turezyn, R. et al J. Biomater Sci. Polym Ed11:217, (2000)) polyampholyte-sodium fluoride and chlorhexidine (WefelJ. S. et al. Am J. Dent. 8, 217-220 (1995); Caufield, P. W. and Navia,J. M. in the Biological Basis of dental caries, Menaker, L. 406-407,Harper and Row, (1980), benzoate-like preserving agents (see Davis, B.A. et al Caries Res 35, 331-337, (2001), Isomalt® (Takatsuka, T. J. DentRes. Sp Iss. A #2815 (2002), silanols (see Loty C et al J. Biomed. Mat.Res. 47; 367 (2000), and dicalcium phosphate dihydrate calcium carbonate(see U.S. Pat. No. 4,556,561 and Cury, J. A. et al Caries Res. 183(2003). Calcium and phosphate are another example (ideally 1.5 m mol/LCa and 0.9 m mol/L PO4) see Exterkate, R. A. M. et al J. Dent Res. 721599-1603 (1993). Examples of suitable calcium compounds are: calciumchloride, calcium bromide, calcium nitrate, calcium acetate, calciumgluconate, calcium benzoate, calcium glycerophosphate, calcium formate,calcium fumarate, calcium lactate, calcium butyrate, calciumisobutyrate, calcium maleate, calcium maleate, calcium propionatecalcium vaerate. Examples of suitable inorganic phosphates are alkalisalts and ammonium salts of orthophosphoric acid such as potassiumsodium or ammonium orthophosphate, monopotassium phosphate, dipotassiumphosphate tripotassium phosphate, monosodium phosphate, disodiumphosphate and trisodium phosphate. Other active agents are (e.g. sodiumlauryl sulphate (to reduce surface tension), azacycloheptane,diphosphonate, triclosan, polyvinyl methylether with maleic anhydridecopolymer resins (see Zhang et al J. Clin. Dent 14: 23-28 (2003)xylitol, erythritol, vitamin E, aloe vera and rigid beta sheet proteinssuch as synthetic polyaspartate and polyglutamate proteins and naturalagents purified from mineralized tissue such as glycoproteinsphosphorylated amino acids and acidic sulfated polysaccharides (seeAddadi et al ACS Symposium series 444; Addadi et al in Chemistry andBiology of Mineralized Tissues, Ed. Slavkin, H. and Price, P. ElsevierSci. Pub. BV 153-162 (1992)), acidic macromolecules associated withhydrophobic macromolecules such as type 1 collagen, alpha and betachiten (see Addadi, L. and Weiner, s. Angen. Chem. Int. Ed. Engl. 31:153-169 (1992)) and other molecules and substances such as arginine,silk and elastin. They can also be inorganic agents such as zirconiumand ferric pretreatments (see Clarkson B. H. et al. J. Dent. Res.60:1912-1920 (1981) or organic solvents such as urea designed to cleanthe carious lesion (see Shellis, R. P. et al Eur. J. Oral Sci 110:392-395, (2002), being part of the system described within the inventionor they can be applied prior to the device application. Other agents canbe commercial cocktails such as GC Tooth Mousse Recaldent™ orexperimental cocktails such as synthetic enamel preparations.

Acidifying, Buffering or pH Regulating Agents

At least one agent can be included in the matrix or matrices to enhancefluoridation, mineralization or remineralization by altering the pH(3-7) (e.g. acidulated phosphate fluoride (derived from sodium fluorideacidulated with a mixture of sodium phosphate monobasic or dibasic, andphosphoric acid or from sodium fluoride, hydrogen fluoride andorthophosphoric acid), H₃PO₄, citric acid, sodium citrate, or sodiumbicarbonate or by inducing buffering with for example calcium carbonate,arginine and polyacrylic acid fully neutralized with alkali metalammonium or (alkylol) amine compound sodium polyacrylate (see U.S. Pat.No. 6,106,811). Furthermore, buffers may be required to enhancecross-linkage of the matrix or matrices (e.g. phosphate buffers at pH6.8). Those knowledgeable in the art will know that more than one stageof buffering may be required prior to the production of the finalproduct in order to facilitate required steps such as cross-linking orcuring, and optimal pH of the final device which can be low 3-4 foroptimal fluoridation remineralization or mineralization or neutral inorder not to etch porcelain and tooth colored restorations. Agents whichinfluence pH can also have important roles such as in the case of theremineralization of dentin which have been reported to only occur afterthe extraction of proteins (see Clarkson, B. H. et al Caries Res 32:357, 1998). Thus, the matrix or matrices could contain for examplelactic acid, acetic acid, phosphoric acid or EDTA in a single matrix oron an external surface layer of a bi or multilayer device. On the otherhand the dentin or enamel could be first primed with such agents using aliquid gel or an etching device, whereby the active agent is an acid,for example 37% phosphoric acid. Such a device could also be used toetch tooth surfaces prior to bonding of dental material. Another type ofdevice could contain both the etching and bonding agent which isactivated and/or cured, for example by water and/or light application(I.R., U.V. visual spectrum or lasers). One side of an interproximaldevice could be inactive and the second side could be an active sitewhich could be used to fill, seal or coat interproximal sites, fissures,pits, lesions, caries, restoration defects or restoration-tooth margindefects. This second side could be a single phase or double phasesystem.

Another novel approach is the introduction of a buffering agent such assodium bicarbonate during remineralization which penetrate into thesubsurface lesion and then function as a buffering agent during acidchallenges (see Tanaka, K. and Iijima, Y. J. of Dent. 29: 421-426(2001)).

The Matrix and Cross-Linking Agents

The role of the matrix or matrices is to carry at least one primaryactive fluoridation mineralizing or remineralizing agent with or withoutat least one enhancing agent or other active agent and to provide therequired viscosity, strength, plasticity and elasticity for applicationas well as the required stability or degradation pattern for thedelivery of the active and any auxiliary agents, in order to provide theoptimal rate and time span of ion or chemical interaction with the toothsurface and to provide a mobile environment for the appropriate ionsand/or other chemicals to reach the tooth surface. Those knowledgeableand skilled in the art can alter the degradation by varying theconcentrations and the degree of curing or cross-linking and type ofcross-linking, or combinations thereof as well as the concentration andtypes of enzyme inhibitors, antimicrobial agents, preservatives andsterilizing agents which can interfere with intra-oral biodegradation.Some degradation properties may not be required in a matrix or partthereof if specific chemical or physical intervention requiresinstantaneous delivery.

The types of possible matrices are wide. They can include agents yetunused for dental treatment and agents such as those used as dentureadhesives, impression materials, temporary, provisional or permanentrestorations, sutures, perio- or surgical packs and periodontal agents(see Dental Therapeutics Digest Odontos Pub Inc.: Kay L. W. Drugs inDentistry, Bristol 1972; O'Brien, W. J. and Ryge, G. An Outline ofDental Materials, Saunders 1978; Steinberg, D et al., J. Dent. Res.67-208 Abstract No. 767, 1988; U.S. Pat. Nos. 5,324,519, 4,938,763,5,278,201, 5,077,049, 5,739,176 and 5,733,950). The matrix or matricesmaterial or materials may be sub-classified into natural products andsynthetic products.

Polysaccharide polymers (e.g. agar, alginates, carboxymethylcellulose,carrageenan, cellulose, gellan gum, Kelcogel®, Kelcogel®F, KelcoBiopolymers, starches and retted flax extracts), lipids, polyisoprenes(e.g. latex rubber and gutta percha), resins and gums (e.g. tragacanthand storax) and proteins (e.g. alpha or beta chitin, soluble elastin andcollagen or denatured collagen in the form of gelatin) are examples ofnatural products. In some cases agents may need to be treated, forexample, dialyzed and de-ionized to remove impurities.

Purified collagen can be untreated or treated with fixing agents toprolong its resistance to digestion (similar to catgut surgical sutureproduction). Denatured collagen can be impregnated with chromium saltsto enhance its tensile strength and retard its absorption. A preferredpolymeric matrix is a gelatin matrix, although those experienced in theart know the method of dissolution of gelatin is highlytechnique-sensitive and the method used can cause considerabledifferences in the texture. Further, gelatin, like collagen, can belysine-cross linked with glutaraldehyde (an organelle preservant whichhas also been used for human aortic valve implants and dental pulptreatments; Kopel, H. M. et al., J. of Dent. for Child 47: 425-430,(1980)) and Periochip®. Another possible cross-linking agent isformaldehyde, which forms intra- and intermolecular methylene bridgesbetween various amino acids. Further examples include but are notlimited to allyl methacrylate, 2,3- or 3,4-dehydroxybenzaldehyde, glycoldimethacrylate, nordihydroguaiacetic acid, rosemarinic acid, strontium,calcium, tannic acid and hexamethylenediisocyanate and chondroitinsulfate. Again, the biocompatibility of these agents must be carefullyexamined even though some of them have been used clinically. Physicalmeans of treating gelatin to induce cross-linking are also possible forexample by microwave-treatment (Vandelli, M. A. et al J. of ControlledRelease 96, 67-84 (2004)). The gelatin may be of any source, for examplebovine or non-mammalian gelatin. Bovine gelatin is preferably used whena matrix or matrices with higher rigidity is required.

It is prudent to note that a completely natural matrix of gelatinwithout cross-linking can also be used with an appropriate cover.Furthermore, natural cross-linkings are also feasible, for examplecalcium and hydroxylysin or leucine, dihydroxylysine or leucine (TraubW., and Piez, K., A. Adv. Protein Chem. 25:243-352, 1971), lysine,arginine, proteins, polysaccharides such as dextran, lipids such assodium docusate and dehydrodihydroxylysine or leucine (Bailey, A. J. etal., Biochem. Biophys. Res. Commun. 35:663-671 (1969)), and enzymaticcross-linking, for example, by transglutaminase (Orban J. M. et al. J ofBiomedical Materials Research 68A:756-762, (2004)).

Likely candidates within the boundary of possible synthetic productsthat may serve for the matrices of this invention are homopolymers orcopolymers with a wide molecular weight range formed by condensation,additional anionic, cationic and/or catalytic polymerization systems.Examples are acrylamide based polymers and a cationic monomer (see U.S.Pat. No. 4,837,007) cyanoacrylates, polycarbonates, polyurethane,polyester urethane dimethacrylate, polycaprolactones, ethyl triglycidemethacrylate, polysulphides, povidone, polyacrylic methacrylic acid,acrylic and modifications such as poly(hydroxyethyl methacrylate),poly(methylmethacrylate) modified with small amounts of ethyl butyl orother alkyl methacrylates, polyethylene glycol, sodium polyacrylate PEG400 and PEG 3350 and other carbomers. Some of these are indeedcommercial or laboratory products such as polymethylvinylether-co-maleicanhydride and polyvinylether-co-maleic anhydride and polyvinylpyrrolidone, carboxymethylcellulose, silated hydroxyethylcellulose orhydroxypropyl methylcellulose (Bourges et al Adv. In Colloid andInterface Sci 215-228: 2002; Bourges X. et al. Biopolymers 63:232-238:2002) aqueous methacrylic polymer formulations for sustained andcontrolled release of dental and other products (e.g. Eudragit® Rohm).These polymers may require activators and cross-linking (see below).However, other agents are at times required, for example retardingagents such as hydroquinone and eugenol. Other yet different examplesare zinc eugenolate, petrolateum and stearyl alcohol. Other gels may beincluded such as Carbopol polymers. (BF Goodrich Noveon) or a Na₂Si 039H2 0 solution mixed with phosphoric acid and hydrofluoric acid (see U.S.Pat. No. 3,679,360).

It is to be appreciated that the degree of cross-linking is of majorsignificance to the rate of release of the active and/or auxiliaryagents. The determination of the degree of cross-linking of thepolymeric matrix or matrices is within the capabilities of the man ofskill in the art of pharmacy. Other factors are antimicrobial agents,preservatives, sterilizing agents inhibitors (such as inhibitors ofmatrix metalloproteinases (see WO 98/16503) and enzyme inhibitors whichslow down the biodegradation of the matrix or matrices.

The matrices of the present invention can be strengthened not only bycross-linking, but also by other methods. For Example, U.S. Pat. No.6,565,960 describes polymer composite compositions in which the polymerfibers, e.g. collagen fibers and gelatin, are strengthened by addingparticular catechol-containing compounds, particularly compounds whichhave two or more catechol groups, to the polymeric material and forminga polymer of the compounds that intercalate within the polymericmaterial, e.g., forming a polymer composite. According to this U.S.patent, it is possible that the resulting polymer forms a scaffold-likestructure throughout the polymeric material without the necessity ofcross-linking the individual polymeric materials, e.g., collagen orgelatin polypeptides. This scaffolding provides synthetic polymer fibershaving a tensile strength, stiffness, and strain at failure that iscomparable to or better than natural polymeric material fibers. As allreferences cited herein, also U.S. Pat. No. 6,565,960 is fully hereinincorporated.

Other novel matrices which can also be used as matrix and sealingagents, for example at pit and fissures, are Sn—Sn catenation, Sn—Clchains or lattices or Sn protein chains (see Jodaikin, A. and Goldstein,S., J. Dent. 16:140-144, (1988)), and even combinations with fluoride,calcium, phosphate and tin (see Harris, N. O. and Christen, A. G.Primary Preventive Dentistry 4^(th) Ed. Norwalk Appleton Longe 1995; Wu.H. et al, abstract from Hua Zi Kou Qiang Yi Xue Za Zhi 18: 219-221,(2000)).

Yet another novelty is a matrix or matrices which is or includes amatrix-bound fluoride ion exchange system which can be ‘recharged’ withfluoride from external sources such as toothpastes, oral rinses, dentalmaterials (see U.S. Pat. No. 5,639,840) and professionally appliedfluoride systems (see Zimmerman, B. F. et al J. Dent. Res. 63:689-692(1984); Fuji 1XGP® fast by GC Inc.).

Although the matrix or matrices are defined as a delivery system, thisinvention does not preclude the use of the matrix or matrices itself asa template or framework to control remineralization or mineralizationbased on control and design principles culled from biologicalmineralization or fabricated synthetic analogs.

Preservatives and Sterilizing Agents

The addition of preservatives and sterilizing agents may be advantageousparticularly for long-dwelling matrices, as they will inhibit thedevelopment of various microorganisms such as bacteria, fungi and yeast,and they could play a role in inhibiting the biodegradation of thematrix or matrices, thereby influencing its longevity and the release ofthe active agent. Examples of preservatives are benzoic acid, biguanide,polyamino propyl biguanide, cetyl pyridinium chloride, phenol,methylparaben, metal proteins (see Horman, H. in Sigel, H. Metal Ions inBiological Systems Vol 3 New York Marcel and Dekker pg 105, 1974 andJodaikin, A. and Goldstein, S. J. Dent 16:140-144, (1988)), and sodiumbicarbonate, sorbic acid, thymol and examples of sterilizing agents areiodine, potassium and alcohol.

Stabilizing Agents

The purpose is to inhibit an unwanted or premature reaction such asreactions of calcium phosphate and fluoride by chemical means orphysical means such as the use of a varnishing, coating or encapsulationagent.

Antimicrobial Agents

Included agents for therapeutic functions can be antibacterial,antiviral, antifungal and other antimicrobial agents. Indeed stannousfluoride has shown antibacterial activity (see Paine, M. L. et al JADA129, 6977, (1998)). Other examples are alexidine, chlorhexidinedigluconate, hexetidine, copper zinc citrate and stannous pyrophosphate,triclosan, cetylpyridinium chloride and halogenated bisphenoleccompounds.

Cleaning Agents

The invention can function as an interproximal site cleaning system asan alternative or supplement to flossing. The invention would thus needto include agents such as a surfactant or sudsing agent which foamthroughout a wide pH range. Examples of cleaning agents are sodium alkylsulfate, sodium lauryl sulfate, sodium coconut monoglyceride sulfonates,sodium lauryl sarcosinate, taurates, sodium lauryl sulfoacetate, sodiumlauroyl isothionate, sodium lauryl carboxylate, sodium dodecylbenzenesulfonate, poloxamers, polyoxyethylene sorbitan esters, fattyalcohol ethoxylates, polyethylene oxide, cocamidoppropyl betaine,hydrogen peroxide, sodium bicarbonate, monosodiumphosphate, sodiumhydroxide, potassium hydroxide, sodium carbonate and imidazole. Anotherpossibility is effervescing agents of systems such as the use of asodium bicarbonate/citric acid system. The effervescing loosens ordislodges interproximal plaque and debris at a microscopic level therebyovercoming flossing which cannot negotiate rough surfaces, especially atthe microscopic level.

Tooth Desensitizing Agents

Examples are fluorides (see above), potassium citrate, potassiumchloride, potassium tartrate, potassium bicarbonate, potassium oxalateand potassium nitrate.

Whitening or Bleaching Agents

Although Whitestrips® by Crest have been marketed as a tooth whiteningsystem in the form of a strip which contains hydrogen peroxide thisinvention includes a system to whiten difficult areas to access such asinterproximal regions. The agents that can be used include hydrogenperoxide, carbamide peroxide, metal chlorites such as calcium chlorite,barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite,potassium chlorite, hypochlorite, perborates, percarbonates, peroxyacids, persulfates, urea peroxide, calcium peroxide, chlorine dioxide,sodium percarbonate, oxones, and even enzymes such as protease (see U.S.Pat. No. 6,521,215). Stabilizing agents may also be required, forexample dipicolinic acid or sodium stannate for peroxy bleaching agents.

Gingiva and Periodontal Agents:

Agents listed in any of the above categories, antimicrobial and cleaningagents can be included, especially chlorhexidine digluconate andhydrogen peroxide (the latter can be combined with baking powder). Otherexamples are hyaluronic acid, thymol, doxycycline, and tetracyclinehydrochloride.

Anticalculus Agents

Examples are alkalimetal pyrophosphates, hypophosphite-containingpolymers, organic phosphonates, and phosphocitrates. Indeed someanti-calculus agents could enhance anticaries activity and improvefluoride availability (see Zhang, Y. P. et al J. Clin. Dent 14: 23-28,(2003)).

Hemostatic Agents

This category includes vasoconstrictors (e.g. adrenalin), absorbableagents (e.g. oxidised cellulose, fibrin, calcium alginate),thromboplastic agents (e.g. thrombin), chemical agents (e.g. aluminumchloride, tannic acid, ferric chloride, ferric sulphate zinc chloride,alum, hyaluronic acid hydrogen peroxide) or physical plugging (e.g. thedevice includes bone wax). The role of a hemostat would be to stopbleeding which could hamper fluoridation or chemical treatment inregions where bleeding is caused by gingival or other bleeding.

Liquid Vehicles

Liquid vehicles may be solvents used particularly when preparing thematrix or matrices or to facilitate application. Examples are water,polydimethylsiloxane, ethyl alcohol or glycerin (glycerol) alone or inany combination.

Plasticisers and Elasticisers

Plasticisers and elasticisers may be used to modify the mechanicalproperties of the matrix or matrices, where needed and desired. Examplesare polyethylene glycol, dibutyl phthalate, glycerol, sorbitol, mineralsalts, olive oil, linseed oil, light mineral oil, polymers of ethylenepropylene, polyolefins, polyacrylates polymethylates, styrene-butadiene,vinyl ethylene acetate copolymers, butadiene isoprene, gum base,silicone resins and gums, silk and elastin for example, purified from anatural rubbery protein from Ligamentum nuchae.

Another example is carboxypolymethylene which can also be incorporatedin the matrix or matrices in order to increase the viscosity of thedevice and reduce the sorption of saliva thereby also influencing thebiodegradation of the device.

According to some embodiments of present invention, the matrix ormatrices may be made from any suitable material as described above, suchas for example gelatin, in combination with an elasticiser, such as forexample soluble elastin, sorbitol or gum base, the gelatin beingpreferably cross-linked and bound to soluble elastin using any suitablematerial such as for example glutaraldehyde, nordihydroguaiaretic acidand/or tannic acid. Such matrices have adequate plastic properties andare at the same time of sufficient toughness to maintain the mechanicalintegrity of the system when affixed at a dental site.

Adhering Agents

Agents may be added to facilitate adhesion to dental surface. Examplesare white wax, bees wax, rosin (colophonium bases), shellac, gum masticand polybutene.

Fillers, Softeners and Binders

The matrix or matrices may also comprise fillers and/or softeners and/orbinders such as beeswax, coconut oil, corn syrup, gum Arabic, gummastic, flour, hydrogenated castor oil, kaolin (aluminum silicate),magnesium oxide, paraffin, silicon dioxide, sodiumcarboxymethyl-cellulose, xanthan gum, zinc oxide or other variousinorganic molecules. It should be noted that certain ions may inhibitremineralization in some cases (for example P₂O₇, HCO₃, SiO₄, CrO₄, Mgand Zn) and some inorganic fillers can be coated with water repellantcoupling agents such as vinyl silane. Examples of softeners are lecithinand waxes.

Coloring or Staining Agents

These include agents to enhance the appearance of the applied at leastone matrix, and dyes which are released to enhance caries detection, asdiscussed above. Examples are fuchsin or acid red 52 in propyleneglycol. These diagnostic dyes include conventional histological stains,clinical decay detection agents and agents whose detection can beenhanced with light, for example fluorescence agents by UV light orother agents activated by intense light within the visual spectrum, oragents drawn by blotting of the lesion after the device or material isremoved and the tooth surface rinsed. A color change system could alsobe used to indicate for example stages of degradation of the device, pHof the site and/or amounts of fluoride at the site. Another applicationof coloring is the need for marking of the surface to be treated with adye in the said device which enhances the effects of lasers such asNd.Yag (Neodymium-Yttrium Aluminum-Garnet lasers, see Miller, M, andTruhe, T. JADA 124:32 (1993)).

Flavoring or Sweetening Agents and Breath Fresheners or Sensates(Warming or Cooling Agents)

A flavoring or sweetening or sensate agent may be added to the matrix ormatrices, for example, menthol, sodium saccharin, sorbitol, aspartame,sodium chloride. Also breath fresheners may be added to the matrix ormatrices, for example parsley seed, methyl salicylate, sunflower oilsand peppermint oil.

It is understood that the invention can include a thickening agent, asudsing agent, a dessicating agent, an anti-plaque agent, ananti-inflammatory agent, humectants, nutrients, an analgesic oranesthetic agent, antioxidants or another therapeutic or cosmetic agentor mixtures thereof for oral and systemic use/uses.

The matrix or matrices is preferably made from a material, such as forexample gelatin cross-linked by glutaraldehyde, nordihydroguaiareticacid and/or tannic acid that is resorbable and/or biodegradable in thesaliva by host enzymes, bacteria or by means of the dissolutionproperties of the saliva or drinks Nonetheless, the matrix or matricesmay alternatively be made from a non-resorbable material which alsoreleases the active material or materials that is being delivered to thetarget area. For example, the matrix or matrices may be made from rubberlatex, a polymer or any one of a large variety of sugars, lipids,nucleic acids or other proteins found in rubber latex bonded to an aminefluoride which is released in the mouth because of, for example, a hostenzyme.

The matrices and devices of this invention and the manufacture thereofare not limited to the above chemical components, but encompass alltheir variations, and include other chemicals as only examples have beenpresented above. Further, the biocompatibility of these agents and theirinteractions need to be carefully examined and tested prior to clinicalapplication.

While some embodiments of the invention have been described by way ofillustration, it will be apparent that the invention can be carried intopractice with many modifications, variations and adaptations, and withthe use of numerous equivalents or alternative solutions that are withinthe scope of persons skilled in the art, without exceeding the scope ofthe claims.

1. A retention device for installation at a dental site, the dental sitecomprising an insertion space at least partially enclosed by twoadjacent facing dental surfaces, and defining an insertion path into theinsertion space, the retention device comprising an installedconfiguration including at least a first device part in a first spatialdisposition with respect to at least a second device part, wherein insaid spatial disposition said first device part is at least one ofrolled, bent or folded with respect to said second device part about arespective reference axis generally parallel to the insertion path, andwherein said first device part and said second device part haverespective outer-facing surfaces, each said outer-facing surface facinga respective one or another of said dental surfaces when the retentiondevice is installed in the insertion space, the retention device beingconfigured in said installed configuration for providing controlleddelivery to said dental site of at least one material having apredetermined intraoral activity via said outer-facing surfaces whensaid retention device is installed in the insertion space and in contactwith said dental surfaces, said retention device comprising at least onematrix containing said material, the retention device further comprisinga pre-installed configuration, in which said first device part is in asecond spatial disposition with respect to said second device part,different from said first spatial disposition, and in which said firstdevice part is correspondingly at least one of unrolled, unbent orunfolded with respect to said second device part about said respectivereference axis.
 2. A retention device according to claim 1, wherein saidreference axis is generally co-extensive with said facing dentalsurfaces.
 3. A retention device according to claim 1, wherein saiddental surfaces are comprised on adjacent teeth.
 4. A retention deviceaccording to claim 1, wherein in said installed configuration, saidfirst device part is generally inclined to said second device part aboutsaid reference axis at an acute angle.
 5. A retention device accordingto claim 1, wherein in said installed configuration, said outer-facingsurfaces are facing directions generally away from one another.
 6. Aretention device according to claim 1, wherein in said pre-installedconfiguration said first device part is in a generally co-planar spatialdisposition with respect to said second device part.
 7. A reshapableretention device according to claim 1, wherein said retention device ismade from a resilient material capable of enabling fixing of theretention device at the dental site.
 8. A retention device according toclaim 1, wherein said device comprises one of the group consisting ofthe following bending facilitators at said reference axis: (a) anindented, bending line; (b) a perforated bending line; (c) a physicalindicating mark along the bending line; and (d) a chemically treatedindicating mark along the bending line.
 9. A retention device accordingto claim 1, wherein the at least one matrix comprises a hydrophilicpolymer such as to enable said retention device to be affixed byswelling in situ by the hydration of said matrix in the oral cavityafter accommodation of said retention device at the dental site.
 10. Aretention device according to claim 1, wherein said retention device ispreferably soft for easy interproximal insertion, and preferablyprovides a cleaning effect which would serve as an alternative orsupplement to flossing and releases at least one antimicrobial orcleansing agent and/or at least one remineralizing or mineralizingagent.
 11. A retention device according to claim 1, wherein saidretention device is one of: substantially biodegradable,self-degradable, substantially resorbable and substantiallynon-resorbable.
 12. A retention device according to claim 1, wherein theat least one matrix further comprises any one of an enhancing agent forenhancing the application and release of the active material such asplasticizer, elasticizer, coloring agents, adhering agent, filler,softener, binder and preserving or sterilizing agent or any one of anauxiliary agent such as an antimicrobial agent, anti plaque agent, antiinflammatory agent, antioxidant, humectants, nutrient analgesic oranaesthetic agent, anti calculus agent, cleaning agent, effervescentagent, tooth desensitizing agent, staining agent, hemostatic agent,astringent agent, whitening or bleaching agent, flavoring or sweeteningagent, breath freshener, or sensate.
 13. A retention device according toclaim 1, wherein the material is selected from the group consisting ofsodium fluoride, stannous fluoride, stannous hexafluorozirconate,calcium fluoride, difluorosilane, hydrogen fluoride, sodiummonofluorophosphate, ytterbium trifluoride, sodium hexafluorosilicate,ammonium fluoride, acidulated phosphate fluoride, an amine fluoride,fluoroahuminosilicate glass and any mixture thereof, or comprises anyother suitable fluoridation agent.
 14. A retention device according toclaim 1, wherein the material is selected from the group consisting ofstannous fluoride, alexidine, chlorhexidine digluconate, hexetidine,copper zinc citrate and stannous pyrophosphate, triclosan,cetylpyridinium chloride and halogenated bisphenolic compounds, orcomprises any other suitable antimicrobial agent.
 15. A retention deviceaccording to claim 1, wherein the material is any one of a cleaningagent, a tooth desensitizing agent and a tooth whitening/bleachingagent.
 16. A retention device for installation at a dental site, thedental site comprising an insertion space at least partially enclosed bytwo adjacent facing dental surfaces, and defining an insertion path intothe insertion space, the retention device having a V-shaped installedconfiguration, comprising at least a first device part disposed withrespect to at least a second device part about a reference axis to formtwo arms of said V-shaped installed configuration, wherein said firstdevice part and said second device part have respective outer-facingsurfaces, each said outer-facing surface configured for facing arespective one or another of said dental surfaces when the retentiondevice is installed in said insertion space, the retention device beingconfigured in said installed configuration for providing controlleddelivery to said dental site of at least one material having apredetermined intraoral activity via said outer-facing surfaces whensaid retention device is installed in the insertion space and in contactwith said dental surfaces, said retention device comprising at least onematrix containing said material, the retention device further comprisinga non-V-shaped pre-installed configuration, in which said first part isin a second spatial disposition with respect to said second part,different from said first spatial disposition.
 17. A retention deviceaccording to claim 16, wherein in said installed configuration, saidfirst device part is generally inclined to said second device part aboutsaid reference axis at an acute angle.
 18. A retention device accordingto claim 16, wherein in said pre-installed configuration said firstdevice part is in a generally co-planar spatial disposition with respectto said second device part.
 19. A retention device according to claim16, wherein said device comprises one of the group consisting of thefollowing bending facilitators at an apex of said V-shaped installedconfiguration: (a) an indented, bending line; (b) a perforated bendingline; (c) a physical indicating mark along the bending line; and (d) achemically treated indicating mark along the bending line.
 20. Aretention device according to claim 16, wherein the at least one matrixcomprises a hydrophilic polymer such as to enable said retention deviceto be affixed by swelling in situ by the hydration of said matrix in theoral cavity after accommodation of said retention device at the dentalsite.
 21. A retention device for installation at a dental site, thedental site comprising an insertion space at least partially enclosed bytwo adjacent facing dental surfaces, and defining an insertion path intothe insertion space, the retention device comprising a reference axisgenerally dividing said device into a first device part and a seconddevice part, each having a respective outer-facing surface configuredfor facing a respective one or another of said dental surfaces, theretention device being configured for being installed in said insertionspace with each said outer-facing surface in contact with a respectiveone or another of said dental surfaces, and further configured forproviding controlled delivery to said dental site of at least onematerial having a predetermined intraoral activity via said outer-facingsurfaces when said retention device is installed in the insertion spaceand in contact with said dental surfaces, said retention devicecomprising at least one matrix containing said material, the retentiondevice further comprising a bending facilitator associated with saidreference axis for facilitating bending or folding said first devicepart with respect to said second device part at said reference axis toprovide an installed configuration.
 22. A retention device according toclaim 21, wherein in said installed configuration, said first devicepart is generally inclined to said second device part about saidreference axis at an acute angle.
 23. A retention device according toclaim 21, wherein in said installed configuration, said outer-facingsurfaces are facing directions generally away from one another.
 24. Aretention device according to claim 21, wherein said device furthercomprises a pre-installed configuration, wherein said first device partis in a generally co-planar spatial disposition with respect to saidsecond device part.
 25. A retention device according to claim 21,wherein said bending facilitator comprises any one of: (a) an indented,bending line; (b) a perforated bending line; (c) a physical indicatingmark along the bending line; and (d) a chemically treated indicatingmark along the bending line.
 26. A retention device according to claim21, wherein the at least one matrix comprises a hydrophilic polymer suchas to enable said retention device to be affixed by swelling in situ bythe hydration of said matrix in the oral cavity after accommodation ofsaid retention device at the dental site.